新兴抗肿瘤靶点EZH2作用机制及研究进展

Mechanism and research progress of EZH2,an emerging antitumor target

zeste基因同源蛋白2(enhancer of zeste homolog 2,EZH2)是由EZH2基因编码的一种赖氨酸特异性组蛋白甲基转移酶(histone-lysine N-methyltransferase,HRX),是多梳家族蛋白(polycomb-group proteins,PcGs)家族的重要组分。该基因正常状态下参与胚胎干细胞发育,维持正常细胞分化,在两性发育中驱动女性一个X染色体的沉默,在造血过程中维持B淋巴细胞和T淋巴细胞的未分化状态。病理状态下,EZH2成为一种基因抑制因子,当它过度表达时,组蛋白的三甲基化导致许多正常开启的肿瘤抑制因子被关闭。在多种肿瘤组织中EZH2含量明显高于癌旁组织,预后差的肿瘤中EZH2表达含量明显高于预后良好的肿瘤。因此,抑制EZH2的表达很可能是未来癌症治疗的一个有希望的策略。本文就目前研究状况做一简要综述。

Enhancer of zeste homolog 2(EZH2)is a histone-lysine N-methyltransferase enzyme(EC 2.1.1.43)encoded by EZH2 gene,which is an important component of polycomb group proteins(PcGs).In normal state,This gene catalyzes trimethylation of H3K27,participates in the development of embryonic stem cells,maintaining cell differentiation,leading to X-inactivation during female development.H3K27me3 is also involved in suppressing genes that promote differentiation,thus maintaining an undifferentiated state of B-and T-cells and playing an important role in regulating hematopoiesis.Under pathological conditions,as a gene suppressor,once it is overexpressed,many tumor suppressor genes that are normally turned on,are turned off.In a wide variety of cancers,EZH2's content in tumor tissue is significantly higher than paracancerous tissue,Increased EZH2 expression is linked to poor patient survival and poor prognosis.Accordingly,EZH2 inhibition might be a promising strategy for future therapies of cancer.This article reviews some current progresses of research results.